chr14-58408549-T-C

Variant names:

• chr14-58408549-T-C
• rs549526864
• NM_207377.3:c.426T>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_207377.3(TOMM20L):​c.426T>C​(p.Asn142Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TOMM20L NM_207377.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

TOMM20L (HGNC:33752): (translocase of outer mitochondrial membrane 20 like) Predicted to enable mitochondrion targeting sequence binding activity. Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix and tRNA import into mitochondrion. Predicted to be integral component of membrane. Predicted to be part of mitochondrial outer membrane translocase complex. Predicted to be integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

TIMM9 (HGNC:11819): (translocase of inner mitochondrial membrane 9) TIMM9 belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]

ENSG00000258378 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOMM20L	NM_207377.3	c.426T>C	p.Asn142Asn	synonymous_variant	Exon 5 of 5	ENST00000360945.7	NP_997260.1
TIMM9	NM_012460.4	c.*485A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000395159.7	NP_036592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TOMM20L	ENST00000360945.7	c.426T>C	p.Asn142Asn	synonymous_variant	Exon 5 of 5	1	NM_207377.3	ENSP00000354204.2
TIMM9	ENST00000395159.7	c.*485A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_012460.4	ENSP00000378588.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251164 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461590 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727080

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.4
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs549526864; hg19: chr14-58875267;